Evidence map›Paper›PMID 41845367›Full record

ArticleMolecular cancer2026

ADAT2-mediated A-to-I tRNA modification promotes oncogenic translation and colorectal cancer progression and chemoresistance.

Cillian H Cheng, Fenfen Ji, Jianming Shen, Ying Jiao, Danyu Chen, Huan Yang, Liufang Ye, Ruizhi Tao, Qinyao Wei, Wei Kang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Cillian H ChengDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.ORCID http://orcid.org/0000-0002-0975-6926
Fenfen JiDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Jianming ShenDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Ying JiaoDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Danyu ChenDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Huan YangDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Liufang YeDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Ruizhi TaoDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Qinyao WeiDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Wei KangDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Jun YuDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. junyu@cuhk.edu.hk.
Chi Chun WongDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. chichun.wong@cuhk.edu.hk.ORCID http://orcid.org/0000-0003-1362-3541

Funding

1+1+1 CUHK-CUHK(SZ)-GDSTC Joint Collaboration Fund 2025A0505000044Heath and Medical Research Fund 08190706, 22210122Noncommunicable Chronic Diseases-National Science and Technology Major Project 2023ZD0501400 and 2023ZD0500200Research Grants Council (RGC)-Collaborative Research Fund C4008-23WF, C4042-24GFRGC-General Research Fund 14101322, 14101725
6 · The paper itself

Abstract

backgroundAdenosine-to-Inosine (A-to-I) modification is one of the most common transfer RNA (tRNA) modifications in humans. However, the role of A-to-I tRNA modification in colorectal cancer (CRC) remains poorly understood.

methodstRNA modification was profiled by LC-MS in paired CRC and adjacent normal tissues (N = 70). The clinical significance of adenosine deaminase tRNA specific 2 (ADAT2) was evaluated using in-house (N = 157) and TCGA cohorts (N = 283). The function of ADAT2 in CRC was determined in intestine-specific ADAT2 knockout mice. Mechanism of ADAT2 was assessed by integrated RNA-sequencing, tRNA-sequencing, and ribosome-sequencing analyses.

resultsAmong 32 tRNA nucleotide modifications, A-to-I modification is the top enriched tRNA modification in CRC tumors compared to paired adjacent normal tissues (P < 0.001). Consistently, A-to-I modification enzyme ADAT2 is elevated in CRC and associated with poor patient survival in independent patient cohorts. Functionally, ADAT2 overexpression promotes malignant phenotypes in CRC cells and patient-derived CRC organoids, whereas ADAT2 knockout exerts opposite effects. Intestine-specific ADAT2 knockout mice showed attenuated colorectal tumorigenesis. Integrated sequencing identified that ADAT2 boosts translation efficiency of genes highly dependent on A-to-I codons, specifically enriched in WNT/β-catenin signaling. We revealed HDAC7 as a downstream target, whereby ADAT2 promotes HDAC7 translation in an A-to-I dependent fashion. HDAC7 interacts with β-catenin, leading to its activation and nuclear translocation. For translational value, ADAT2 promotes chemoresistance in CRC, and targeting ADAT2 by VNP-encapsulated ADAT2-siRNA promoted Oxaliplatin and 5-Fluorouracil efficacy to suppress CRC growth.

conclusionsADAT2-driven tRNA A-to-I modification promotes CRC tumorigenesis and chemoresistance via HDAC7-WNT/β-catenin axis, and is an independent prognostic factor.

Indexed as

Colorectal NeoplasmsDrug Resistance, NeoplasmProtein BiosynthesisRNA, TransferAnimalsCell Line, TumorDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMiceMice, KnockoutRNA, TransferADAT2ChemoresistanceColorectal cancertRNA modification

Identifiers

PMID41845367
PMCPMC13107624

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.